



Patented Dec. '7, 1948 TED (OFFICE n LoGENATEnrrRaNooMrouNDs AND P ODUQJI HEREQ i i David Gwyn Jones and John George Mackay 3 'Bremner,Norton-on-Tees, England, assignoi's i i to Imperial Chemical IndustriesLimited, a corporation of Great Bri ain No Drawing. Application my 11,1946, Serial No. Great Britain J ulyll, 194 5 i i aolaimst ;(01. w en);

This invention relates to the preparatibnof halogenated pyran compounds.

We have found that;2,3-dihydropyran and substitution derivatives thereoirea t with bromine or chlorine and a 'hydrox-yl-containing organiccompound ROI-I or such a compound in which thaihrdrosen of the hydr xyle upt s placed by an alkali metal to form respectivelyracom pound of theformula (wherein X represents bromine or chlorine and Riis an aliphaticalicyclic, aromatic or heterocyclic group) and substitution derivativesthereof. 7 Examples of substituent groups are: hydrocarbon, carbonyl,carbonyl, carboxylic-ester, particularly aliphatic monocarboxylic ester,halogen and ether groups.

"The reaction proceeds smoothly at atmospheric temperature and pressurebut higher tempera turesand pressures may be used if desired. Withchlorine further substitution may take place if the temperaturebecomestoo 1 high and it is thereforepreferred to operate attemperaturesnot much in excess of 100 C. The reactants are employed instoichiometric proportions, but an assess theh ltgeam r Some es e d Itis frequently convenient to employ an excess of the hydroigylcontain ingcompound. The reaction may bef illustrated by theequationz H! H2CHaOH-I-Clz-I-HaC CH H2O CHCI A H01 H H H2 OCH:

It is advantageous to conduct the reaction in the presence of a basicsubstance, e. g. sodium carbonate or calcium carbonate in order toneutralise the hydrogen halide formed during the reaction, which wouldpromote a side reaction. If a good yield of the desired substance is tobe obtained a basic substance should be present. A suflicient amount ofthe basic substance should be present to keep the reaction mixturealways alkaline.

Instead of chlorine or bromine compounds such as for example, tertiarybutyl hypochlorite or bromonitro-methane, which yield halogen under theconditions of the reaction, may be used, and instead of a hydroxylcontaining compound there may be used metal alcoholates, such as forexample sodlummethoxide.

The-reaction maybetvcarried out in the presence of water, but itispreferable to work under substantially anhydrous conditions.

and .i furfuryl' alcohol. If desired an excess.

of the hydroxyl-containing compound maybe employed. it

By theprocess of the invention there can be obtained the following whichare all believed to be new tetrahydropyran derivatives: z-methoxy.

3-ch1ortetrahydropyran: from dihydropyran and methanol; 2unethcxy-Sa-brom 3 carbmethoxytetrahydropyran from the methyl ester of2,3- dihydropyran-S-carboxylic acid and methanol;

ZsmethoxyHB, 3-dlch1or tetrahydropyran from chlordih dropyran andmethanol; and 5-methy 2@methoxye3t-chlortetrahydropyran from methyldihydropyranand methanol. 0! these Z-meth oxy-B chlortetrahydropyran hasa B. P. of 38-40 C./2 mm. and R. I. a 1.4576;and2-methoxy-B,3edichlortetrahydropyran has a B. P. of 40-4? C./2 mm.

These new tetrahydropyra n derivatives may be represented by thefollowing structural formula:

fi OXR' RH CHOR wherein R is a radical from the group consisting of-CH3, CsH5,

R is a radical from the group consisting of Br, -Cl, and -COOCHs; R" isa radical from the group consisting of -H and -CH3, and X is a. radicalfrom the group consisting of --Br and -C1.

The invention is illustrated but not limited by the following examples.

Example 1 16.8 grams of dihydropyran was dissolved in 280 ccs. methanoland the solution was stirred with 40 grams calcium carbonate while 4.5litres at normal temperature and pressure of chlorine were added, thetemperature of the reaction mixture being below 10 C.

2-methoXy-3-chlortetrahydropyran was obtained as a reaction product.

Example 2 19.7 grams of chlordihydropyran and 30 grams of sodiumcarbonate were stirred in 75 cos. of methanol, and 4 litres of chlorinemeasured at N. T. P. were passed into the solution. The reaction mixturewas filtered and the filtrate distilled giving 2-methoxy-3, 3-dichlortetrahydroyran.

Example 3 14.2 grams of the methyl ester of2,3-dihydropyran-5-carboxylic acid and 60 gms. of calcium carbonate werestirred in 300 mls. of methanol and there was added to the mixture 16gms. of bromine in methanol solution. Care was taken to keep thetemperature of the mixture below C. When the reaction, as judged bybromine absorption, appeared to be complete, the slurry was filtered andthe filtrate was evaporated.

There was obtained in 30% yield methoxybrom-carbmethoxy tetrahydropyran,which had a boiling point of 138 C. at 20 mm. absolute pressure andwhich, when recrystallised from methanol, had a melting point of 253-254C. This is believed to be 2-methoxy-3-brom-3-carbmethoxytetrahydropyran.

We claim:

1. The process for the production of tetrahydropyran derivatives whichcomprises reacting a compound from the group consisting of 2,3-dihydropyran, methyl dihydropyran, chlorodihydropyran and 2,3dihydropyran-B-carboxylio acid with a halogen from the group consistingof chlorine and bromine and with a compound from the group consisting ofcompounds having the formula ROH and said compounds in which thehydrogen of the hydroxyl group is replaced by an alkali metal wherein, Ris from the group consisting of alkyl, aryl, furfuryl, andtetrahydrofurfuryl radicals in the presence of a basic compound whichneutralizes the hydrohalide formed during the reaction.

2. The process of claim 1 in which the reaction is carried out at atemperature less than 100 C. under anhydrous conditions.

3. The process for the production of z-methoxy- 3-chlontetrahydropyranwhich comprises reacting dihydropyran with chlorine and methyl alcoholin the presence of a basic compound which neutralizes the hydrohalideformedduring the reaction. :2

4. The process for the production of Z-methoxy 3 brom 3-carblmethoxy-tetrahydropyran which comprises reacting the methyl esterof 2,3- dihydropyran 5 oarboxylic acid with bromine and methyl alcoholin the presence of a basic compound which neutralizes the hydrohalideformed during the reaction.

5. The process for the production of 5-methyl-2-methoxy-3-chlortetrahydropyran which comprises reacting methyldihydropyran with chlorine and methyl alcohol in the presence of a basiccompound which neutralizes the hydrahalide formed during the reaction.

6. New tetrahydropyran derivatives of the formula 1 wherein R. is aradical from the group consisting) and -om-oncmornomo R is a radicalfrom the group consisting of -Br, -C1, and COOCH3; R" is a radical fromthe group consisting of -H and --CH3, and X is a radical from the groupconsisting of -Br and.

7. As a new chemical compound 2-methoxy JOHN GEORGE MACKAY BREMER.

REFERENCES CITED The following references are of record in the file ofthis patent:

Paul, Bull. Soc. Chem. 5, 1397 (1934). West et 8.1., J. Biol. Chem. 122,605 (1938).

